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Long-term protection and mechanism of pacing-induced postconditioning in the heart
Brief periods of ventricular pacing during the early reperfusion phase (pacing-induced postconditioning, PPC) have been shown to reduce infarct size as measured after 2 h of reperfusion. In this study, we investigated (1) whether PPC leads to maintained reduction in infarct size, (2) whether abnorma...
Autores principales: | , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Springer-Verlag
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2862957/ https://www.ncbi.nlm.nih.gov/pubmed/20336304 http://dx.doi.org/10.1007/s00395-010-0095-2 |
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author | Babiker, Fawzi A. Lorenzen-Schmidt, Ilka Mokelke, Eric Vanagt, Ward Y. Delhaas, Tammo Waltenberger, Johannes Cleutjens, Jack P. Prinzen, Frits W. |
author_facet | Babiker, Fawzi A. Lorenzen-Schmidt, Ilka Mokelke, Eric Vanagt, Ward Y. Delhaas, Tammo Waltenberger, Johannes Cleutjens, Jack P. Prinzen, Frits W. |
author_sort | Babiker, Fawzi A. |
collection | PubMed |
description | Brief periods of ventricular pacing during the early reperfusion phase (pacing-induced postconditioning, PPC) have been shown to reduce infarct size as measured after 2 h of reperfusion. In this study, we investigated (1) whether PPC leads to maintained reduction in infarct size, (2) whether abnormal mechanical load due to asynchronous activation is the trigger for PPC and (3) the signaling pathways that are involved in PPC. Rabbit hearts were subjected to 30 min of coronary occlusion in vivo, followed by 6 weeks of reperfusion. PPC consisted of ten 30-s intervals of left ventricular (LV) pacing, starting at reperfusion. PPC reduced infarct size (TTC staining) normalized to area at risk, from 49.0 ± 3.3% in control to 22.9 ± 5.7% in PPC rabbits. In isolated ejecting rabbit hearts, replacing LV pacing by biventricular pacing abolished the protective effect of PPC, whereas ten 30-s periods of high preload provided a protective effect similar to PPC. The protective effect of PPC was neither affected by the adenosine receptor blocker 8-SPT nor by the angiotensin II receptor blocker candesartan, but was abrogated by the cytoskeletal microtubule-disrupting agent colchicine. Blockers of the mitochondrial K(ATP) channel (5HD), PKC (chelerythrine) and PI3-kinase (wortmannin) all abrogated the protection provided by PPC. In the in situ pig heart, PPC reduced infarct size from 35 ± 4 to 16 ± 12%, a protection which was abolished by the stretch-activated channel blocker gadolinium. No infarct size reduction was achieved if PPC application was delayed by 5 min or if only five pacing cycles were used. The present study indicates that (1) PPC permanently reduces myocardial injury, (2) abnormal mechanical loading is a more likely trigger for PPC than electrical stimulation or G-coupled receptor stimulation and (3) PPC may share downstream pathways with other modes of cardioprotection. |
format | Text |
id | pubmed-2862957 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | Springer-Verlag |
record_format | MEDLINE/PubMed |
spelling | pubmed-28629572010-05-04 Long-term protection and mechanism of pacing-induced postconditioning in the heart Babiker, Fawzi A. Lorenzen-Schmidt, Ilka Mokelke, Eric Vanagt, Ward Y. Delhaas, Tammo Waltenberger, Johannes Cleutjens, Jack P. Prinzen, Frits W. Basic Res Cardiol Original Contribution Brief periods of ventricular pacing during the early reperfusion phase (pacing-induced postconditioning, PPC) have been shown to reduce infarct size as measured after 2 h of reperfusion. In this study, we investigated (1) whether PPC leads to maintained reduction in infarct size, (2) whether abnormal mechanical load due to asynchronous activation is the trigger for PPC and (3) the signaling pathways that are involved in PPC. Rabbit hearts were subjected to 30 min of coronary occlusion in vivo, followed by 6 weeks of reperfusion. PPC consisted of ten 30-s intervals of left ventricular (LV) pacing, starting at reperfusion. PPC reduced infarct size (TTC staining) normalized to area at risk, from 49.0 ± 3.3% in control to 22.9 ± 5.7% in PPC rabbits. In isolated ejecting rabbit hearts, replacing LV pacing by biventricular pacing abolished the protective effect of PPC, whereas ten 30-s periods of high preload provided a protective effect similar to PPC. The protective effect of PPC was neither affected by the adenosine receptor blocker 8-SPT nor by the angiotensin II receptor blocker candesartan, but was abrogated by the cytoskeletal microtubule-disrupting agent colchicine. Blockers of the mitochondrial K(ATP) channel (5HD), PKC (chelerythrine) and PI3-kinase (wortmannin) all abrogated the protection provided by PPC. In the in situ pig heart, PPC reduced infarct size from 35 ± 4 to 16 ± 12%, a protection which was abolished by the stretch-activated channel blocker gadolinium. No infarct size reduction was achieved if PPC application was delayed by 5 min or if only five pacing cycles were used. The present study indicates that (1) PPC permanently reduces myocardial injury, (2) abnormal mechanical loading is a more likely trigger for PPC than electrical stimulation or G-coupled receptor stimulation and (3) PPC may share downstream pathways with other modes of cardioprotection. Springer-Verlag 2010-03-25 2010 /pmc/articles/PMC2862957/ /pubmed/20336304 http://dx.doi.org/10.1007/s00395-010-0095-2 Text en © The Author(s) 2010 https://creativecommons.org/licenses/by-nc/4.0/ This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited. |
spellingShingle | Original Contribution Babiker, Fawzi A. Lorenzen-Schmidt, Ilka Mokelke, Eric Vanagt, Ward Y. Delhaas, Tammo Waltenberger, Johannes Cleutjens, Jack P. Prinzen, Frits W. Long-term protection and mechanism of pacing-induced postconditioning in the heart |
title | Long-term protection and mechanism of pacing-induced postconditioning in the heart |
title_full | Long-term protection and mechanism of pacing-induced postconditioning in the heart |
title_fullStr | Long-term protection and mechanism of pacing-induced postconditioning in the heart |
title_full_unstemmed | Long-term protection and mechanism of pacing-induced postconditioning in the heart |
title_short | Long-term protection and mechanism of pacing-induced postconditioning in the heart |
title_sort | long-term protection and mechanism of pacing-induced postconditioning in the heart |
topic | Original Contribution |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2862957/ https://www.ncbi.nlm.nih.gov/pubmed/20336304 http://dx.doi.org/10.1007/s00395-010-0095-2 |
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